RESUMO

Post-stroke depression (PSD) is one of the most frequent complications of stroke. The Yi-nao-jie-yu prescription (YNJYP) is an herbal prescription widely used as a therapeutic agent against PSD in traditional Chinese medicine. Disruption of adult neurogenesis has attracted attention as a potential cause of cognitive pathophysiology in neurological and psychiatric disorders. The Notch signaling pathway plays an important role in neurogenesis. This study investigated the effects of YNJYP on adult neurogenesis and explored its underlying molecular mechanism in a rat model of PSD that is established by middle cerebral artery occlusion and accompanied by chronic immobilization stress for 1 week. At 2, 4, and 8 weeks, depression-like behavior was evaluated by a forced swim test (FST) and sucrose consumption test (SCT). Neurogenesis was observed by double immunofluorescence staining. Notch signals were detected by real-time polymerase chain reaction. The results show that, at 4 weeks, the immobility time in the FST for rats in the PSD group increased and the sucrose preference in the SCT decreased compared with that in the stroke group. Therefore, YNJYP decreased the immobility time and increased the sucrose preference of the PSD rats. Further, PSD interfered with neurogenesis and decreased the differentiation toward neurons of newly born cells in the hippocampal dentate gyrus, and increased the differentiation toward astrocytes, effects that were reversed by YNJYP, particularly at 4 weeks. At 2 weeks, compared with the stroke group, expression of target gene Hes5 mRNA transcripts in the PSD group decreased, but increased after treatment with YNJYP. At 4 weeks, compared with the stroke group, the expression of Notch receptor Notch1 mRNA transcripts in the PSD group decreased, but also increased after treatment with YNJYP. Overall, this study indicated that disturbed nerve regeneration, including the increased numbers of astrocytes and decrease numbers of neurons, is a mechanism of PSD, and Notch signaling genes dynamically regulate neurogenesis. Moreover, YNJYP can relieve depressive behavior in PSD rats, and exerts a positive effect on neurogenesis by dynamically regulating the expression of Notch signaling genes.

RESUMO

Ischemic stroke is one of the main causes of death and disablement globally. The NLR family pyrin domain containing 3 (NLRP3) inflammasome is established as a sensor of detecting cellular damage and modulating inflammatory responses to injury during the progress of ischemic stroke. Inhibiting or blocking the NLRP3 inflammasome at different stages, including expression, assembly, and secretion, may have great promise to improve the neurological deficits during ischemic stroke. The current review provides a comprehensive summary of the current understanding in the literature of the molecular structure, expression, and assembly of the NLRP3 inflammasome, and highlights its potential as a novel therapeutic target for ischemic stroke.

RESUMO

BACKGROUND: Glycosylphosphatidylinositol (GPI) anchoring is a special type of protein posttranslational modification, by which proteins with diverse function are attached to cell membrane through a covalent linkage between the protein and the glycolipid. Phosphatidylinositol glycan anchor biosynthesis class A (PIGA) is a key enzyme in GPI anchor biosynthesis, somatic mutations or genetic variants of which have been associated with paroxysmal nocturnal hemoglobinuria (PNH), or PIGA deficiency, respectively. More than 10 PIGA pathogenic or likely pathogenic variants have been reported in a wide spectrum of clinical syndromes of PIGA deficiency, including multiple congenital anomalies hypotonia-seizures syndrome 2 (MCAHS2). METHODS: Whole-exome sequencing (WES) was performed on two trios, that is., the proband's family and his affected maternal cousin's family, from a nonconsanguineous Chinese family pedigree with hypotonia-encephalopathy-seizures disease history and putative X-linked recessive inheritance. Sanger sequencing for PIGA variant was performed on affected members as well as unaffected members in the family pedigree to verify its familial segregation. RESULTS: A novel likely pathogenic variant in PIGA was identified through comparative WES analysis of the two affected families. The single-nucleotide substitution (NC_000023.9:g.15343279T>C) is located in intron 3 of the PIGA gene and within the splice acceptor consensus sequence (NM_002641.3:c.849-5A>G). Even though we have not performed RNA studies, in silico tools predict that this intronic variant may alter normal splicing, causing a four base pair insertion which creates a frameshift and a premature stop codon at position 297 (NP_002632.1:p.(Arg283Serfs*15)). Sanger sequencing analysis of the extended family members confirmed the presence of the variant and its X-linked inheritance. CONCLUSION: WES data analysis along with familial segregation of a rare intronic variant are suggestive of a diagnosis of X-liked PIGA deficiency with clinical features of MCAHS2.

RESUMO

Information about changes in, and causes of, land use/land cover (LULC) is crucial for land use resource planning. We investigated the processes involved in LULC change (LUCC) in the Dongjiang Watershed, in Southern China, over a 15-year period to gain a better understanding of the causes of the main types of LUCC. Using a depth transition matrix and redundancy analysis (RDA), the major types and causes of LUCC for each LULC type over the past 15 years were identified. LUCC exhibited obvious net change, relatively low persistence, and high swap change. The swap changes in most LULC types were considered as a strong signal of LULC transformations. The driving forces behind swap changes were quantified and identified through RDA. The results showed that all driving forces played important roles in explaining swap changes of LULC, although the relative effects of these drivers varied widely with both LULC type and time period. Swap changes of the LULC types were generally classified into two categories. Some, e.g., built-up land and wetland, were affected mostly by landform and/or distance factors, while others, e.g., grassland and woodland, were modulated mostly by climate and/or socioeconomic factors. Selected spatial driving forces and local land use policies played important roles in explaining the dominant LUCC types, but on different timescales. These findings may improve understanding of the detailed processes involved in LUCC, landscape transformation, and the causes of LUCC in other areas with extensive LUCC and could help managers plan, design, and implement land resource management.

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